Primary biliary cirrhosis (PBC) is a progressive liver diseases believed to be of autoimmune nature. Its etiology is unknown. It is characterized by progressive intrahepatic cholestasis as a result of ongoing non-suppurative destructive cholangitis that affecting small intrahepatic bile ducts. Several trials have been conducted to study the effect of immunosuppressants in PBC including methotrexate (MTX). Ten patients with symptomatic PBC were treated in an open label pilot study of oral MTX (15 mg/week). Two remain on therapy after 3 and 5 years respectively, while the drug was stopped in the remaining patients after 1 to 2 years because of apparent lack of effect. A trial that studies the effect of 7.5 vs 15 mg per week of oral MTX was started. Patients were randomized to receive one of the two doses and stratified according tot he presence or absence of symptoms. 19 Symptomatic and 10 asymptomatic patients have been entered in to this trial. Preliminary observations indicate that patients with advanced disease (stages III or IV) do not seem to respond to MTX. Patients with earlier stages (I, II and "early" III) appear to have a better response with a decrease in the activity of serum aminotransferases and alkaline phosphatase and histological improvement.